Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 Cardiovascular and sympatho-adrenal responsiveness to mental stress (CWT; a colour word test), orthostatic testing (ORT) and a cold pressor test (CPT) were examined in three groups of hypertensive patients (n = 14-16) before and after 6 months treatment with metoprolol (243 +/- 26 mg daily), propranolol (149 +/- 16 mg daily) or hydrochlorothiazide (50 +/- 8 mg daily) in an open trial design. 2 Treatment reduced outpatient blood pressures in the three groups similarly (from approximately 155/102 to 135/90 mm Hg). During treatment resting blood pressures in the laboratory were clearly reduced by beta-adrenoceptor blockade but not by thiazide treatment. Metoprolol and propranolol caused similar reductions of basal heart rates and plasma glycerol levels, whereas only propranolol reduced cyclic AMP concentrations in plasma. 3 Before treatment CWT and CPT increased systolic and diastolic blood pressures by about 30%. Heart rate increased by about 30 beats min-1 during CWT and 10-15 beats min-1 during CPT and ORT. Small venous plasma adrenaline responses were evoked by all tests, whereas noradrenaline was elevated mainly by CPT and ORT. Dopamine levels did not change. 4 Heart rate responses to all stressors were markedly and similarly reduced, whereas blood pressure responses were essentially unchanged during metoprolol or propranolol treatment. In the thiazide group circulatory responses to CWT were slightly attenuated, whereas responses to ORT and CPT were unchanged. 5 The systolic blood pressure levels were reduced throughout the test session in all three groups, although less so in the hydrochlorothiazide group. Both beta-adrenoceptor antagonists clearly reduced diastolic blood pressure and heart rate levels at rest and during stress, whereas thiazide treatment caused no significant changes in these respects. 6 The rate pressure product, which increased by 80-100% in response to CWT before treatment, was more markedly reduced by beta-adrenoceptor blockade than by thiazide treatment both at rest and during stress. 7 Self ratings (visual analogue scales) of stress and irritation were increased by CWT in a similar fashion before and during treatment in all groups. beta-adrenoceptor blockade was associated with higher subjective ratings of tiredness at rest, but not after CWT. Performance in the CWT increased slightly more in the thiazide group. The physiological responses to CWT were not correlated to the subjective responses.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Responses to mental stress and physical provocations before and during long term treatment of hypertensive patients with beta-adrenoceptor blockers or hydrochlorothiazide. 288 86

A 91-year-old woman had decreased systemic blood pressure accompanied by dyspnea and general fatigue after resection of a face tumor (Merkel cell carcinoma). Dopamine was administered to elevate systemic blood pressure, but it did not sufficiently restore the hemodynamic status. Left ventricular apical aneurysm was observed on echocardiogram. Furthermore, SAM (systolic anterior movement of the mitral valve) was observed on M-mode echocardiogram and a pressure gradient of 34.6 mmHg in the midventricular position was confirmed by continuous wave Doppler using the Bernoulli equation. After volume overload and discontinuation of dopamine, SAM completely disappeared and midventricular pressure gradient markedly decreased. Her general condition improved. Because of the narrowed outflow tract, hypercontractile state induced by beta adrenergic stimulation seemed to be one of the important factors for the genesis of SAM and pressure gradient.
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PMID:[Intra-ventricular pressure gradient and systolic anterior movement of the mitral valve associated with administration of dopamine in a 91-year-old patient]. 820 77

Feeding is a complex process responsive to sensory information related to sight and smell of food, previous feeding experiences, satiety signals elicited by ingestion and hormonal signals related to energy balance. Dopamine released in specific brain regions is associated with pleasurable and rewarding events and may reinforce positive aspects of feeding. Dopamine also influences initiation and coordination of motor activity and is required for sensorimotor functions. Thus, dopamine may facilitate integration of sensory cues related to hunger, initiating the search for food and its consumption. Dopaminergic neurons in the substantia nigra and ventral tegmental area project to the caudate putamen and nucleus accumbens, where they modulate movement and reward. There are projections from the nucleus accumbens to the lateral hypothalamus that regulate feeding. Dopamine-deficient mice (Dbh(Th/+), Th-/-; hereafter DD mice) cannot synthesize dopamine in dopaminergic neurons. They gradually become aphagic and die of starvation. Daily treatment of DD mice with L-3,4-dihydroxyphenylalanine (L-DOPA) transiently restores brain dopamine, locomotion and feeding. Leptin-null (Lep(ob/ob)) mice exhibit obesity, decreased energy expenditure and hyperphagia. As the hypothalamic leptin-melanocortin pathway appears to regulate appetite and metabolism, we generated mice lacking both dopamine and leptin (DD x Lep(ob/ob)) to determine if leptin deficiency overcomes the aphagia of DD mice. DD x Lep(ob/ob) mice became obese when treated daily with L-DOPA, but when L-DOPA treatment was terminated the double mutants were capable of movement, but did not feed. Our data show that dopamine is required for feeding in leptin-null mice.
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PMID:Dopamine is required for hyperphagia in Lep(ob/ob) mice. 1080 66

Dopamine agonists are becoming increasingly important in the treatment of early and advanced symptoms of Parkinson disease (PD). Although dopamine agonists are known to increase somnolence, their effect on fatigue and the relationship between fatigue and somnolence have not been investigated thoroughly. The objective of this study is to quantitatively measure fatigue in patients with PD treated with dopamine agonists and to correlate fatigue with somnolence. Fifteen patients with PD (mean age, 60.6 +/- 9.7 years; mean disease duration, 4.1 +/- 1.9 years) underwent a continuous (30-second) motor task using four muscle groups before and after 3 months of treatment with dopamine agonists. A fatigue index, defined as the decay of maximal force during continuous exercise, was calculated. Findings were compared with 15 healthy, age-matched control subjects. Patients also completed the Multidimensional Fatigue Inventory (MFI), the Epworth Sleepiness Scale (ESS), and the Hamilton Depression Scale at the same time points. Mean fatigue index (FI) before treatment was significantly higher in PD patients than controls (31.37% +/- 3.81% vs. 23.39% +/- 3.03%, P < 0.001). There was no significant between-group difference after 3 months of treatment. There was no difference in FI of the more affected side before and after treatment (33.33% +/- 6.18% vs. 34.08% +/- 5.43%, P > 0.1). No significant change in MFI scores were noted after treatment, although scores on the ESS increased significantly (6.6 +/- 2.63 vs. 11.7 +/- 5.16; P < 0.05). Fatigue is prevalent in patients with PD but is not influenced by dopamine agonists. Somnolence cannot be attributed to the increase in fatigability and apparently involves a different mechanism.
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PMID:Effect of dopamine agonists on fatigue and somnolence in Parkinson's disease. 1668 90

Goal-directed actions are sensitive to work-related response costs, and dopamine in nucleus accumbens is thought to modulate the exertion of effort in motivated behavior. Dopamine-rich striatal areas such as nucleus accumbens also contain high numbers of adenosine A(2A) receptors, and, for that reason, the behavioral and neurochemical effects of the adenosine A(2A) receptor agonist CGS 21680 [2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine] were investigated. Stimulation of accumbens adenosine A(2A) receptors disrupted performance of an instrumental task with high work demands (i.e., an interval lever-pressing schedule with a ratio requirement attached) but had little effect on a task with a lower work requirement. Immunohistochemical studies revealed that accumbens neurons that project to the ventral pallidum showed adenosine A(2A) receptors immunoreactivity. Moreover, activation of accumbens A(2A) receptors by local injections of CGS 21680 increased extracellular GABA levels in the ventral pallidum. Combined contralateral injections of CGS 21680 into the accumbens and the GABA(A) agonist muscimol into ventral pallidum (i.e., "disconnection" methods) also impaired response output, indicating that these structures are part of a common neural circuitry regulating the exertion of effort. Thus, accumbens adenosine A(2A) receptors appear to regulate behavioral activation and effort-related processes by modulating the activity of the ventral striatopallidal pathway. Research on the effort-related functions of these forebrain systems may lead to a greater understanding of pathological features of motivation, such as psychomotor slowing, anergia, and fatigue in depression.
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PMID:Nucleus accumbens adenosine A2A receptors regulate exertion of effort by acting on the ventral striatopallidal pathway. 1876 98

A 58-year-old previously healthy man presented with diplopia of rapid onset over a few days. Examination demonstrated bilateral sixth and right fourth cranial nerve palsy. MR imaging showed a large sellar mass with significant destruction of the pituitary fossa. Laboratory tests revealed very high serum prolactin (2,483 ng/dl, reference range 3-13 ng/dl). Dopamine agonist therapy was initiated with significant decline in PRL levels; however, nausea, fatigue, and anorexia developed. Within a few weeks the patient developed renal failure and hypercalcemia. Urine protein electrophoresis revealed large free monoclonal kappa peaks while extensive plasmocytosis was evident in bone marrow aspirates. On bone scan numerous lytic lesions were present. A transsphenoidal excisional biopsy was performed which demonstrated two distinct populations of cells, corresponding to a plasma cell tumor and a lactotroph adenoma. Treatment for multiple myeloma was initiated along with radiotherapy for the sellar tumor. Only a few cases of solitary plasmocytomas of the pituitary region have been reported. Few cases of prolactinomas coexisting with other sellar tumors has been described. We discuss in this report possible pathogenic and functional connections between these two tumors. We suggest that in the presence of extensive cranial nerve involvement, atypical imaging findings for a pituitary adenoma and severe hyperprolactinemia, the possibility of a collision tumor should lead the physician to consider excisional tumor biopsy or surgery in addition to dopamine agonist therapy.
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PMID:An unusual collision tumor comprising a prolactinoma and a plasmocytoma originating from the sellar region. 1884 27

The scientific evidence is reviewed for the involvement of the brain monoamines serotonin, dopamine and noradrenaline (norepinephrine) in the onset of fatigue, in both normal and high ambient temperatures. The main focus is the pharmacological manipulations used to explore the central fatigue hypothesis. The original central fatigue hypothesis emphasizes that an exercise-induced increase in serotonin is responsible for the development of fatigue. However, several pharmacological studies attempted and failed to alter exercise capacity through changes in serotonergic neurotransmission in humans, indicating that the role of serotonin is often overrated. Recent studies, investigating the inhibition of the reuptake of both dopamine and noradrenaline, were capable of detecting changes in performance, specifically when ambient temperature was high. Dopamine and noradrenaline are prominent in innervated areas of the hypothalamus, therefore changes in the catecholaminergic concentrations may also be expected to be involved with the regulation of body core temperature during exercise in the heat. Evidence from different studies suggests that it is very unlikely that one neurotransmitter system is responsible for the appearance of central fatigue. The exact mechanism of fatigue is not known; presumably a complex interplay between both peripheral and central factors induces fatigue. Central fatigue will be determined by the collaboration of the different neurotransmitter systems, with the most important role possibly being for the catecholamines dopamine and noradrenaline.
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PMID:Alterations in central fatigue by pharmacological manipulations of neurotransmitters in normal and high ambient temperature. 2019 21

Dopamine modulates executive function, including sustaining cognitive control during mental fatigue. Using event-related functional magnetic resonance imaging (fMRI) during the color-word Stroop task, we aimed to model mental fatigue with repeated task exposures in 33 cocaine abusers and 20 healthy controls. During such mental fatigue (indicated by increased errors, and decreased post-error slowing and dorsal anterior cingulate response to error as a function of time-on-task), healthy individuals showed increased activity in the dopaminergic midbrain to error. Cocaine abusers, characterized by disrupted dopamine neurotransmission, showed an opposite pattern of response. This midbrain fMRI activity with repetition was further correlated with objective indices of endogenous motivation in all subjects: a state measure (task reaction time) and a trait measure (dopamine D2 receptor availability in caudate, as revealed by positron emission tomography data collected in a subset of this sample, which directly points to a contribution of dopamine to these results). In a second sample of 14 cocaine abusers and 15 controls, administration of an indirect dopamine agonist, methylphenidate, reversed these midbrain responses in both groups, possibly indicating normalization of response in cocaine abusers because of restoration of dopamine signaling but degradation of response in healthy controls owing to excessive dopamine signaling. Together, these multimodal imaging findings suggest a novel involvement of the dopaminergic midbrain in sustaining motivation during fatigue. This region might provide a useful target for strengthening self-control and/or endogenous motivation in addiction.
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PMID:Dopaminergic involvement during mental fatigue in health and cocaine addiction. 2309 80

Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper.
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PMID:Dopamine agonist withdrawal syndrome: implications for patient care. 2368 24

Prolactinomas are common pituitary tumors that can cause gonadal dysfunction and infertility related to hyperprolactinemia. Dopamine agonists are the first-line treatment in these patients. Cabergoline leads to significant reduction in serum prolactin levels and tumor size in patients with prolactinoma. Dopamine agonists have been associated with adverse effects such as nausea, vomiting and psychosis. We report here a case with cabergoline-induced immune hemolytic anemia. The patient had cabergoline treatment history for prolactinoma and presented with weakness, fatigue, nausea, and paleness. Laboratory findings revealed severe anemia-related immune hemolysis. There were no causes identified to explain hemolytic anemia except cabergoline. Therefore, cabergoline therapy was stopped and subsequently hemolytic anemia resolved and did not occur again. This is the first reported pediatric case with prolactinoma and cabergoline-induced hemolytic anemia. Clinicians should be watchful for this rare side effect induced by cabergoline.
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PMID:The first report of cabergoline-induced immune hemolytic anemia in an adolescent with prolactinoma. 2394 26


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